Ultrasound
Ultrasound is commonly the first imaging modality used for investigation of neck masses. Paragangliomas of the neck appear as homogeneously hypoechoic masses. Multidirectional hypervascularity is the discerning feature on Doppler imaging (Fig. 1) [14].
CT
Small paragangliomas appear as homogeneous masses, whereas larger paragangliomas can be heterogenous in appearance [15]. There is intense uniform enhancement following intravenous administration of contrast agent in keeping with the hypervascular nature of the tumour [16]. The location of the tumour aids further characterisation, e.g. carotid body tumours cause splaying of the internal and external carotid arteries, and jugulotympanic tumours result in bony erosion (Fig. 2). Punctate calcification or focal areas of high attenuation caused by acute haemorrhage may also be seen in some tumours [17].
MRI
Paragangliomas are usually of low to intermediate signal on T1-weighted images and intermediate to high signal on T2-weighted images (Fig. 3). The hypervascularity results in multiple serpentine areas of signal void [18], which results in the characteristic “salt and pepper” appearance. The high signal areas, or “salt”, are due to slow flow or haemorrhage, and the low signal areas, or “pepper”, are due to the signal voids from high flow on T1- and T2-weighted sequences [19]. The high flow areas are better demonstrated on 3D time of flight sequences where they show high signal intensity [16]. As with CT, the tumours show avid homogeneous enhancement.
SDHB presentation and tumour characteristics
The precise incidence rate of SDH mutations is unknown. SDHB and SDHD mutations have similar prevalence and are more common compared to SDHC, which is rare [20].
SDHB mutation more commonly results in the formation of paragangliomas associated with the sympathetic system [20, 21]. These are predominantly extra-adrenal paragangliomas of the thorax and abdomen (Fig. 4), and less commonly intra-adrenal paragangliomas or pheochromocytomas. There is an increased risk of malignant paragangliomas and metastatic disease with SDHB mutation (Fig. 5) [21, 22]. Other than metastasis there are no specific features of malignancy; however, rapidity of growth and surrounding tissue invasion are suggestive. Extraparaganglial malignancies such as papillary thyroid carcinoma and renal cell carcinoma are also more prevalent in this group [20].
The age at paraganglioma diagnosis is reported at approximately 30 years [20–22].
SDHD presentation and tumour characteristics
SDHD mutations are associated with parasympathetic extra-adrenal paragangliomas [20, 22]. This predominantly results in head and neck tumours, which are usually benign (Fig. 6). There is an increased chance of multifocality (Figs. 7 and 8), but malignancy and metastatic disease are infrequent [20, 22]. As with SDHB mutations, pheochromocytomas are less common.
The age at paraganglioma diagnosis is similar to SDHB at approximately 30 years [20, 22].
SDHB versus SDHD
Although SDHB and D mutations can be broadly divided into the categories above, it is important to remember that there can be overlap with tumour presentation. SDHB mutuations can result in head and neck paraganglioma formation, and SDHD mutations can develop thoracic and abdominal extra-adrenal paragangliomas [12, 23]. Both mutations can result in pheochromocytoma formation. The radiologist should be aware of this when reporting screening investigations for these patients.
SDHA and SDHC
SDHA mutations have been described in Leigh syndrome, a metabolic neurodegenerative disorder [24], and are not currently recognised to result in paraganglioma formation. SDHC mutations are rare and result in head and neck paraganglioma formation [12]. These tumours are usually benign and seldom multifocal [25]. Very rarely do SDHC mutations result in pheochromocytoma formation.
SDHB and SDHD relevance
The recent advances in genetics with regards to SDH mutations have implications for radiology. The radiological diagnosis of a paraganglioma or pheochromocytoma should result in a full genetic workup. Included in this is the imaging of susceptible family members for paragangliomas [7]. This can have a significant impact on the workload of a radiological department. SDH mutation-positive patients need ongoing screening as they are at high risk for developing paragangliomas, pheochromocytomas and further multifocal extraganglial tumours. In this context close collaboration with the local genetics department is essential. Following patient and family member interview and counselling, genetic mutation can be determined from a peripheral blood sample. The family history and type of tumour will determine which mutation is tested for initially.
Imaging protocols
A universal approach to screening is the subject of ongoing work. In a recent review article [12], Timmers et al. recommended MRI of the neck, chest, abdomen and pelvis every 1–2 years. This should be tailored according to individual needs and the specific mutation. In cases of SDHB mutation screening as early as 10 years of age is recommended. Further functional imaging may also be required along with annual history, examination and biochemical testing [26]. Local imaging guidelines should be developed in conjunction with the local genetics departments according to imaging availability and experience. Currently MRI of the head, neck, chest, abdomen and pelvis is the first line investigation in our practice. Subsequent follow-up may be performed with ultrasound or MRI. Post-treatment imaging in our institution is determined by the nature of the intervention on an individual patient basis.